The mammalian eye is the richest source of zinc (per weight of tissue) in the body. The trace metal, which is present in large concentrations in the retina, undoubtedly subserves a variety of functions, one being an essential constituent for activity of alcohol dehydrogenase. Other zinc dependent reactions and processes have not been investigated systematically. It is recognized that chemical compounds with strong metal chelating properties, including at least one drug in clinical use, have evoked multiple deleterious effects on retinal morphology and function in man and experimental animals. Currently, it is not clear which retinal cell types are directly affected by chelators; nor is it known with any degree of certainly if zinc sequestration is the actual event which precipitates retinal damage. We propose to investigate retinal zinc by a series of experiments designed to determine where zinc is, how much, and what happens when its concentration is altered. Our approach emphasizes: measuring by quantitative chemical analyses the trace metals of the retina; locating zinc by light and electron microscopy; correlating the cytological distribution of zinc with retinal stimulation; and studying the changes in retinal morphology and responsiveness to light after treatment with chelators. The results of these experiments should provide much needed information on the utilization of zinc by the cells of the retina, and the extent to which the metal may serve as a locus for drug action.